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Gene expression profiling was used to explore the role of Nef in HIV. Nef induces a transcriptional program in T cells that is 97% identical to that of anti-CD3 T cell activation. This program is inhibited in the presence of cyclosporin. A requirement for TCR zeta and ZAP-70 is demonstrated for formation of the complete profile. Among eight factors particular to the anti-CD3 activation profile are IL16 and YY1, negative regulators of HIV transcription. In contrast, Nef exclusively upregulates factors positively regulating HIV, including Tat-SF1, U1 SNRNP, and IRF-2. New genes associated with Nef include CDK9, the induction of which enhances Tat function. Thus, Nef acts as a master switch early in the viral life cycle, forcing an environment conducive to dynamic viral production.

Type

Journal article

Journal

Immunity

Publication Date

06/2001

Volume

14

Pages

763 - 777

Keywords

Cyclin-Dependent Kinase 9, Cyclin-Dependent Kinases, Cyclosporine, Gene Expression Profiling, Gene Products, nef, HIV-1, Humans, Immunosuppressive Agents, Jurkat Cells, Lymphocyte Activation, Membrane Proteins, Protein-Tyrosine Kinases, Receptor-CD3 Complex, Antigen, T-Cell, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Transcription, Genetic, Virulence, ZAP-70 Protein-Tyrosine Kinase, nef Gene Products, Human Immunodeficiency Virus